Thioureido N-acetyllactosamine derivatives as potent galectin-7 and 9N inhibitors

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Abstract

Derivatives of N-acetyllactosamine carrying structurally diverse thioureido groups at galactose C3 were prepared from a C3'-azido N-acetyllactosamine derivative in a three-step reaction sequence involving azide reduction and isothiocyanate formation by thiophosgene treatment of the C3-amine, followed by reaction of the isothiocyanate with a panel of amines. Evaluation of the N-acetyllactosamine thioureas as inhibitors against galectins-1, 3, 7, 8N (N-terminal domain), and 9N (N-terminal domain) revealed thiourea-mediated affinity enhancements for galectins-1, 3, 7, and 9N. In particular, good inhibitors were discovered against galectin-7 and 9N (K-d 23 and 47 mu M, respectively, for a 3-pyridylinethylthiourea derivative), which represents more than an order of magnitude affinity enhancement over the parent natural N-acetyllactosamine. (c) 2005 Elsevier Ltd. All rights reserved.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area
  • Immunology in the medical area

Keywords

  • N-acetyllactosamine, thiourea, galectin, inhibitor
Original languageEnglish
Pages (from-to)1215-1220
JournalBioorganic & Medicinal Chemistry
Volume14
Issue number4
Publication statusPublished - 2006
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Microbiology, Immunology and Glycobiology - MIG (013025200), Organic chemistry (S/LTH) (011001240)